Association of Education and Depressive Symptoms with Tooth Loss.

Previous evidence suggests the association of lower educational attainment and depressive symptoms with tooth loss. The hypothesis of this study was that these factors may exacerbate the effect on tooth loss beyond the sum of their individual effects. We aimed to clarify the independent and interactive effects of educational attainment and depressive symptoms on the number of missing teeth among community residents. Cross-sectional data of 9,647 individuals were collected from the general Japanese population. Dental examination was conducted by dentists. Educational attainment was categorized into 3 levels based on the number of educational years: ≤9, >9 to ≤12, and >12 y. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depressive symptoms; a total score of ≥16 and/or the use of medications for depression indicate the presence of depressive symptoms. In the multivariate analysis with adjustment for conventional risk factors, educational attainment was identified as a determinant of the number of missing teeth (>9 to ≤12 y of education: coefficient = 0.199, 95% confidence interval [CI], 0.135 to 0.263, P < 0.001; ≤9 y of education: coefficient = 0.318, 95% CI, 0.231 to 0.405, P < 0.001: reference, >12 y of education). An analysis that included interaction terms revealed that the relationship between "≤9 y of education" and the number of missing teeth differed depending on the depressive symptoms, indicating a positive interactive association (coefficient for interaction = 0.198; 95% CI, 0.033 to 0.364, P for interaction = 0.019: reference, >12 y of education). Our study suggests the presence of a significant association between educational attainment and tooth loss, as well as a partial interactive association between "≤9 y of education" and "depressive symptoms" in the general Japanese population.

Short-duration post CT-guided thoracic biopsy monitoring- clinical experience with 440 patients.

PURPOSE: With several studies recording a higher percentage of complications in the first hour of post-biopsy, this study sought to evaluate the safety in the reduction in post-biopsy patient monitoring time after computed tomography (CT)-guided thoracic biopsies, providing a basis for further research. MATERIALS AND METHODS: This was a retrospective study involving patients who were referred to our centre for CT-guided thoracic biopsies from January 2010 to December 2017. Patients who presented with no complications immediately after the post-biopsy CT scan were given 30 min of post-biopsy care after which they were discharged, and given a hot line to call in case of any complication. There was also a follow-up call by a nurse after 24 h to inquire about any complication and general condition of the patients. RESULTS: A total of 440 core needle thoracic biopsies were performed within the period of the study. The most common thoracic region indicated for biopsy was mediastinal (n = 240, 54.5%), followed by lung (n = 185, 42.0%). Complications were recorded at a rate of 6.4% (n = 28), with 4.1% (n = 18) been pneumothorax and pulmonary haemorrhage and haemoptysis accounting for 2.3% (n = 10). No relevant complications were recorded in patients who presented with no complications immediately after the post-biopsy CT scan (n = 374, 85%). CONCLUSIONS: Findings from this initial study have shown that thirty minutes of post-biopsy care could be sufficient for patients present with no complications immediately after a post-procedural scan in CT-guided thoracic biopsies; providing a basis for similar algorithms to be explored in a randomised control study to substantiate the observation.

Frequency and risk factors of thoracic metastases and optimisation of the use of cross-sectional chest imaging in follow-up patients with cervical cancer.

AIM: To optimise cross-sectional chest imaging usage by identifying frequency and risk factors associated with thoracic metastases in cervical cancer patients after initial definitive treatment. MATERIALS AND METHODS: This study, conducted during 2004-2015, examined 361 consecutive patients with histopathologically proven cervical carcinoma with at least 1 year of follow-up. Electronic medical records and all available imaging modes were used to record and assess patient and tumour characteristics and timing of thoracic metastases. Associations with these characteristics and thoracic metastases were assessed using univariate and multivariable Cox proportional hazards modelling. RESULTS: Of the 361 patients, 31 developed thoracic metastases. Multivariate regression results showed that adeno/adenosquamous carcinomas (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.06 to 5.72), other histology (HR, 5.61; 95% CI, 1.81 to 17.42), high International Federation of Gynaecology and Obstetrics (FIGO) stage (HR, 2.84; 95% CI, 1.09 to 7.37), and presence of initial intra-abdominal lymph node metastases (HR, 2.46; 95% CI, 1.02 to 5.90) were associated significantly and independently with thoracic metastases. The second analysis among the subgroup of surgical treatment identified intermediate-high risk classification of recurrence (HR, 5.12; 95% CI, 1.14 to 22.94), high FIGO stage (HR, 2.73; 95% CI, 1.05 to 7.13), and other histology (HR, 11.51; 95% CI, 3.66 to 36.19) as independent predictors of thoracic metastases. Two of the 361 and 2/313 patients with thoracic metastases who did not correspond to the conditions above were in the respective evaluation groups. CONCLUSION: Assessment of negative prognostic factors for thoracic metastases might contribute to reduced need for chest cross-sectional chest computed tomography examinations.

Approximate Bayesian computation analysis of EST-associated microsatellites indicates that the broadleaved evergreen tree Castanopsis sieboldii survived the Last Glacial Maximum in multiple refugia in Japan.

Climatic changes have played major roles in plants' evolutionary history. Glacial oscillations have been particularly important, but some of their effects on plants' populations are poorly understood, including the numbers and locations of refugia in Asian warm temperate zones. In the present study, we investigated the demographic history of the broadleaved evergreen tree species Castanopsis sieboldii (Fagaceae) during the last glacial period in Japan. We used approximate Bayesian computation (ABC) for model comparison and parameter estimation for the demographic modeling using 27 EST-associated microsatellites. We also performed the species distribution modeling (SDM). The results strongly support a demographic scenario that the Ryukyu Islands and the western parts in the main islands (Kyushu and western Shikoku) were derived from separate refugia and the eastern parts in the main islands and the Japan Sea groups were diverged from the western parts prior to the coldest stage of the Last Glacial Maximum (LGM). Our data indicate that multiple refugia survived at least one in the Ryukyu Islands, and the other three regions of the western and eastern parts and around the Japan Sea of the main islands of Japan during the LGM. The SDM analysis also suggests the potential habitats under LGM climate conditions were mainly located along the Pacific Ocean side of the coastal region. Our ABC-based study helps efforts resolve the demographic history of a dominant species in warm temperate broadleaved forests during and after the last glacial period, which provides a basic model for future phylogeographical studies using this approach.

Development of Duodenal Ulcers due to the Discontinuation of Proton Pump Inhibitors After the Induction of Sofosbuvir Plus Ledipasvir Therapy: A Report of Two Cases.

Sofosbuvir plus ledipasvir (SOF-LDV) combination therapy is a promising therapy for post-transplant hepatitis C virus (HCV) reinfection. It is known that gastric pH elevation induces lower absorption of ledipasvir; therefore, the use of proton pump inhibitors (PPIs) should be considered regarding dose reduction after SOF-LDV therapy induction. Here, we report two patients who developed duodenal ulcers due to the discontinuation of PPIs after the induction of SOF-LDV therapy for post-transplant HCV reinfection. The first patient was a 71-year-old man who had undergone living donor liver transplantation due to HCV-related liver cirrhosis. Lansoprazole, 30 mg daily, was discontinued upon SOF-LDV therapy induction. Seven days after SOF-LDV therapy induction, gastrointestinal endoscopy revealed the presence of a duodenal ulcer. The second patient was a 54-year-old man who had undergone living donor liver transplantation due to HCV-related end-stage liver disease. Similar to the first patient, rabeprazole sodium was discontinued upon the induction of SOF-LDV therapy. Eighteen days after SOF-LDV therapy induction, gastrointestinal endoscopy revealed the presence of a duodenal ulcer. In both cases, these duodenal ulcers improved after the resumption of the administration of PPIs, and a sustained virologic response at 12 weeks was achieved by SOF-LDV therapy with PPI use. Thus, PPI use should be continued consistently during SOF-LDV therapy for post-transplant HCV reinfection.

MOB1-YAP1/TAZ-NKX2.1 axis controls bronchioalveolar cell differentiation, adhesion and tumour formation.

Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway. These proteins, which coactivate LArge Tumour Suppressor homologue kinases, are also tumour suppressors. To investigate MOB1A/B's roles in normal physiology and lung cancer, we generated doxycycline (Dox)-inducible, bronchioalveolar epithelium-specific, null mutations of MOB1A/B in mice (SPC-rtTA/(tetO)7-Cre/Mob1aflox/flox/Mob1b-/-; termed luMob1DKO mice). Most mutants (70%) receiving Dox in utero (luMob1DKO (E6.5-18.5) mice) died of hypoxia within 1 h post-birth. Their alveolar epithelial cells showed increased proliferation, impaired YAP1/TAZ-dependent differentiation and decreased surfactant protein production, all features characteristic of human respiratory distress syndrome. Intriguingly, mutant mice that received Dox postnatally (luMob1DKO (P21-41) mice) did not develop spontaneous lung adenocarcinomas, and urethane treatment-induced lung tumour formation was decreased (rather than increased). Lungs of luMob1DKO (P21-41) mice exhibited increased detachment of bronchiolar epithelial cells and decreased numbers of the bronchioalveolar stem cells thought to initiate lung adenocarcinomas. YAP1/TAZ-NKX2.1-dependent expression of collagen XVII, a key hemidesmosome component, was also reduced. Thus, a MOB1-YAP1/TAZ-NKX2.1 axis is essential for normal lung homeostasis and expression of the collagen XVII protein necessary for alveolar stem cell maintenance in the lung niche.

Recurrent Hepatitis B and D Virus Infection in a Liver Transplant Recipient.

Hepatitis B virus (HBV) and hepatitis delta virus (HDV) co-infections progress rapidly and lead to cirrhosis. In Japan, the prevalence of HBV and HDV co-infected patients is low. Therefore, there are few reports of patients with HBV and HDV co-infection having undergone liver transplantation. Herein, we report a rare case of recurrence of HBV and HDV in a 41-year-old man who underwent living donor liver transplantation 4 years prior.

Comparison of human mesenchymal stem cells derived from bone marrow, synovial fluid, adult dental pulp, and exfoliated deciduous tooth pulp.

Populations of pluripotent stem cells were isolated from bone marrow, synovial fluid, adult dental pulp, and exfoliated deciduous teeth and their multipotentiality properties compared. Osteogenic, chondrogenic, adipogenic, and neurogenic differentiation potentials were examined. Bone marrow mesenchymal stem cells (BMMSCs) and synovial fluid-derived cells (SFCs) showed the highest levels of osteogenesis as expressed by alkaline phosphatase (ALP) activity (0.54±0.094 U/mg protein and 0.57±0.039 U/mg protein, respectively; P=0.60) and by osteocalcin (BGLAP; determined by real-time RT-PCR). SFCs showed the highest levels of chondrogenesis as expressed by ALP activity (1.75±0.097 U/mg protein) and of COL2A1 and COL10A1 by real-time PCR. In terms of adipogenesis, lipid vesicles were observed in the BMMSCs and SFCs. Dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED) exhibited neurogenesis potential, as shown by increases in expression of class III ß-tubulin (TUBB3) and microtubule-associated protein 2 (MAP2) on RT-PCR. Variability was found in the differentiation potential corresponding to the tendency of the original tissue to differentiate. It is suggested that the cell type should be selected depending on the regenerative treatment regimen.

Impact of Donor and Recipient Single Nucleotide Polymorphisms in Living Liver Donor Transplantation for Hepatitis C.

INTRODUCTION: Recently, several studies have shown that specific single nucleotide polymorphisms (SNPs) affect liver fibrosis progression in patients with hepatitis C virus (HCV) infection. In this study, we examined the impact of donor and recipient SNPs on the progression of fibrosis after liver transplantation for HCV infection. METHODS: This cohort study enrolled 43 patients with HCV infection who underwent liver transplantation at our hospital. We evaluated 5 genotypes (rs4374383, rs2629751, rs9380516, rs8099917, and rs738409) that have been reported to be significant predictors of fibrosis in HCV infection using a Taqman assay. RESULTS: Liver fibrosis (stage ≥ F1, New Inuyama classification) was detected at 1 year after liver transplantation in 30 cases (70%). The rs2629751 non-AA-genotype was found to be significantly associated with fibrosis progression at 1 year after liver transplantation (AA:GG or GA = 46%:88%, P < .05). The primary outcome was stage ≥F2 (portoportal septa) or liver-related mortality in 22 patients. The time to stage ≥F2 fibrosis or liver-related mortality was significantly different only in terms of the donor rs2629751 genotype (AA:GG or GA = 5.5 ± 0.6 years:3.6 ± 0.7 years, P = .025). CONCLUSIONS: The rs2629751 genotype may be an important predictor of posttransplant outcome in HCV-infected patients. This result might be useful in donor selection for liver transplantation in HCV-infected patients and may guide therapeutic decisions regarding early antiviral treatment.

Post-operative infection of endoscopic submucosal dissection of early colorectal neoplasms: a case-controlled study using a Japanese database.

WHAT IS KNOWN AND OBJECTIVE: Endoscopic submucosal dissection of early colorectal neoplasms (ESD-ECN) is known to be an operation with risk of contamination, possibly requiring pre-operative antimicrobial prophylaxis for the prevention of post-operative infection. However, an evaluation of the need for pre-operative antimicrobial prophylaxis for ESD-ECN has yet to be reported. The objective of this study was to determine whether pre-operative antimicrobial prophylaxis is associated with a reduced incidence of post-operative infection following ESD-ECN. METHODS: The present retrospective case-controlled study utilized a database built from the medical records of 14 university hospitals throughout Japan. Patients who were admitted and discharged from the hospital from April 2012 to October 2013 and who had undergone ESD-ECN were included in the study. Patients who had been undergone any other operation during their course of hospitalization, and patients who were prescribed antimicrobial agents for reasons other than post-operative infection or for prophylaxis were excluded. Characteristics of the study population, pre-operative antimicrobial prophylaxis and antimicrobial therapy for post-operative infection were investigated. In addition, we compared the characteristics of patients with post-operative infection (PI) and those with no post-operative infection (NPI). Univariate analyses were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS AND DISCUSSION: We obtained the records of 522 patients who had undergone ESD-ECN from the database. After application of exclusion criteria, 421 patients were enrolled. The post-operative infection rate was 1·2%. Peritonitis was found most to be the most common post-operative infection (44%). Pre-operative antimicrobial prophylaxis was used for 314 patients (75%), with a median duration of 3·0 (range 1-11) days. Cefotiam was most frequently prescribed for pre-operative antimicrobial prophylaxis (56%). Antimicrobial therapies were started 1-10 days after ESD-ECN for a duration of 1-14 days. Pre-operative antimicrobial prophylaxis was not associated with post-operative infection rate, with an OR (95% CI) of 0·73 (0·08-6·61). However, digestive tract perforation was shown to be associated with post-operative infection and had an OR (95% CI) of 17·1 (1·66-176·45). WHAT IS NEW AND CONCLUSION: Post-operative infection is an exceedingly rare event following ESD-ECN. Pre-operative antimicrobial prophylaxis had no significant effect on post-operative infection following ESD-ECN and thus may be unnecessary. Instead, prevention of digestive tract perforation may be more critical for the decrease in post-operative infections.

The population demography of Betula maximowicziana, a cool-temperate tree species in Japan, in relation to the last glacial period: its admixture-like genetic structure is the result of simple population splitting not admixing.

Conservation of the local genetic variation and evolutionary integrity of economically and ecologically important trees is a key aspect of studies involving forest genetics, and a population demographic history of the target species provides valuable information for this purpose. Here, the genetic structure of 48 populations of Betula maximowicziana was assessed using 12 expressed sequence tag-simple sequence repeat (EST-SSR) markers. Genetic diversity was lower in northern populations than southern ones and structure analysis revealed three groups: northern and southern clusters and an admixed group. Eleven more genomic-SSR loci were added and the demographic history of these three groups was inferred by approximate Bayesian computation (ABC). The ABC revealed that a simple split scenario was much more likely than isolation with admixture, suggesting that the admixture-like structure detected in this species was due to ancestral polymorphisms. The ABC analysis suggested that the population growth and divergence of the three groups occurred 96 800 (95% CI, 20 500-599 000) and 28 300 (95% CI, 8700-98 400) years ago, respectively. We need to be aware of several sources of uncertainty in the inference such as assumptions about the generation time, overlapping of generations, confidence intervals of the estimated parameters and the assumed model in the ABC. However, the results of the ABC together with the model-based maps of reconstructed past species distribution and palaeoecological data suggested that the modern genetic structure of B. maximowicziana originated prior to the last glacial maximum (LGM) and that some populations survived in the northern range even during the LGM.

Leptin improves fatty liver independently of insulin sensitization and appetite suppression in hepatocyte-specific Pten-deficient mice with insulin hypersensitivity.

Nonalcoholic fatty liver disease (NAFLD) is recognized as the hepatic component of the metabolic syndrome. Although NAFLD is a major cause of cirrhosis and cancer of the liver of unknown cause, no established pharmacological treatment for NAFLD has been established yet. It has been reported that leptin treatment improved fatty liver dramatically as well as insulin resistance and hyperphagia in patients with lipodystrophy. However, it is unclear whether leptin improves fatty liver independently of these metabolic improvements. We investigated the liver effect of leptin independently of insulin sensitization and appetite suppression using hepatocyte-specific Pten-deficient (AlbCrePtenff) mouse, a model of severe fatty liver with insulin hypersensitivity. Male AlbCrePtenff mice were infused subcutaneously with leptin (20 ng/g/h) for 2 weeks using osmotic minipumps. Leptin infusion effectively reduced liver weight, liver triglyceride content, and glutamate pyruvate transaminase (GPT) concentrations as well as food intake and body weight without the change of plasma insulin concentration in AlbCrePtenff mice. Pair-feeding also reduced body weight but not liver triglyceride content. Pair feeding reduced α1 and α2 AMP-activated protein kinase (AMPK) activities and PGC1α gene expression in the liver, while leptin infusion unchanged them. The present study clearly demonstrated that leptin improve fatty liver independently of insulin sensitization and suppression of food intake. It was suggested that leptin improves fatty liver by stimulation of ß-oxidation in the liver. The present study might provide a further understanding on the mechanism of metabolic effect of leptin.

Sleep disturbances and quality of life in patients after living donor liver transplantation.

BACKGROUND: Following improvements in patient and graft survival after liver transplantation (LT), the recipients' quality of life has become an important focus of patient care. Sleep is closely related to physical and mental health; however, sleep disturbances in LT patients have not yet been evaluated. METHODS: We assessed 59 LT patients (aged ≥18 years) between September 2011 and September 2012. The patients completed the restless legs syndrome (RLS), 36-item short-form health survey (SF-36), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) questionnaires. In addition, laboratory data were obtained and neuropsychological tests (NPT) were performed during study entry. RESULTS: Thirty-eight patients (64%) were included in the poor sleep group (PSQI ≥6 or ESS ≥10). The SF-36 scores were lower in the poor sleep group than in the good sleep group. Eleven patients (18%) had RLS. An NPT score ≥3 indicated minimal hepatic encephalopathy (MHE3). The MHE3 group consisted of 22 patients (43%). The time after LT was shorter; serum albumin, branched chain amino acid/tyrosine molar ratio (BTR), and role limitations due to poor physical health were lower; and serum ammonia levels were higher in the MHE3 group than in the MHE0-2 group. When the poor sleep group was divided into subgroups (control, MHE, RLS, and unknown), MHE patients had high model for end-stage liver disease scores, high ammonia levels, and low BTR, whereas RLS patients showed a short time after LT. CONCLUSION: Sixty-four percent of recipients were classified as poor sleepers. SF-36 scores were lower for poor sleepers than good sleepers. RLS and MHE are major diseases that cause sleep disturbances in patients after LT.

Analysis of the hepatic functional reserve, portal hypertension, and prognosis of patients with human immunodeficiency virus/hepatitis C virus coinfection through contaminated blood products in Japan.

BACKGROUND: As the survival of human immunodeficiency virus (HIV)-infected individuals has improved due to the widespread use of antiretroviral therapy, the mortality rate due to hepatitis C virus (HCV)-related liver disease has increased in HIV/HCV-coinfected patients. AIM: The aims of this study were to establish the appropriate therapeutic strategy for HIV/HCV-coinfected patients by evaluating the liver function, including the hepatic functional reserve and portal hypertension, and to investigate the prognosis of HIV/HCV-coinfected patients in Japan. PATIENTS AND METHODS: In addition to regular liver function tests, the hepatic functional reserve of 41 patients with HIV/HCV coinfection was evaluated using the indocyanine green retention rate and liver galactosyl serum albumin-scintigraphy. The data for 146 patients with HIV/HCV coinfection through blood products were extracted from 4 major HIV centers in Japan. In addition to liver function tests, the platelet counts (PLT) were evaluated as a marker of portal hypertension. RESULTS: In spite of the relatively preserved general liver function test results, approximately 40% of the HIV/HCV-coinfected patients had an impaired hepatic functional reserve. In addition, while the albumin and bilirubin levels were normal, the PLT was <150,000/µL in 17 patients. Compared with HCV mono-infected patients with a PLT <150,000/µL, the survival of HIV/HCV-coinfected patients was shorter (HCV, 5 years, 97%; 10 years, 86% and HIV/HCV, 5 years, 87%; 10 years, 73%; P < .05). CONCLUSION: These results must be taken into account to establish an optimal therapeutic strategy, including the appropriate timing of liver transplantation in HIV/HCV-coinfected patients in Japan.

A subtype prediction score for primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. Although adrenal venous sampling (AVS) is recommended as the gold standard procedure for subtype classification in PA, it is a specialized technique with limited availability. The objective of this study was to develop a scoring system that predicted PA subtype using clinical characteristics. Seventy-one patients with PA were studied. The subjects were diagnosed as having either unilateral (n=32) or bilateral disease (n=39) based on AVS, surgery and/or the postoperative clinical course. Variables associated with laterality in the univariate analysis were entered into multivariable logistic regression models and the regression coefficients were used to construct a subtype prediction score. The diagnostic significance of the score was then evaluated using receiver operating characteristic (ROC) curve analysis. The subtype prediction score was calculated as follows: serum potassium ⩽3.4 mEq l(-1), 2 points; plasma aldosterone concentration ⩾165 pg ml(-1), 3 points; and aldosterone to renin ratio ⩾1000 in a post-captopril challenge test (plasma renin activity in ng ml(-1) h(-1)), 3 points. ROC curve analysis for the ability to discriminate between unilateral and bilateral PA showed that a score of 5 points had 75% sensitivity and 95% specificity, and a score of 3 points had a sensitivity of 97% and a specificity of 59%. The area under the ROC curve was 0.920 (95% confidence interval, 0.859-0.979). Our subtype prediction score could discriminate between unilateral and bilateral PA and is useful for selecting patients who should undergo AVS before surgery.

Significance of background coloration in endoscopic detection of early esophageal squamous cell carcinoma.

Endoscopic diagnostics of early squamous cell carcinoma (SCC) in the laryngo-esophageal region have dramatically improved together with development of less invasive endoscopic treatment. It is essential for gastrointestinal endoscopists to detect lesions when they are still endoscopically treatable, especially in this region since surgical approach can still be extremely invasive. Pioneers have found some notable fundamental alterations in early SCC and created several classifications. Inoue [Dig Endosc 2001;13(suppl): 40-41] proposed the intrapapillary capillary (IPCL) classification, which focused on the microvascular change of the mucosal surface. One of the significances of this classification is that it clearly distinguished the lesions that require further pathological evaluation by categorizing the diameter change of the IPCLs. On the other hand, Arima et al. [Esophagus 2005;2:191-197] advocated the alteration of microvessels as well as change of the vascular arrangement in the area. Most recently, the Japan Esophageal Society constructed a new classification uniting these two exemplary classifications as the 'Japanese Classification of Magnifying Endoscopy for Early Squamous Cell Carcinoma'. This classification was intended to be simple and easily applicable in general clinical practice. Brownish color change between the IPCLs has reported to be one of the useful findings in distinguishing early SCC from benign changes such as inflammatory change and low-grade intraepithelial neoplasia. Nevertheless, the exact cause of this phenomenon remains unclear. We recently examined the association of color change with hemoglobin (Hb) in cancer tissue, since NBI exclusively detects the wavelength of Hb in superficial vessels in the gastrointestinal tract. This review article also describes our examination of a distinct finding in esophageal cancer, namely, 'background coloration'.